The present invention is related to certain photodynamic, topically-applicable medicaments and methods for treatment of human or animal tissue using photodynamic therapy (PDT).
PDT was originally developed to treat cancer and other diseases with the promise of limiting the invasiveness of the therapeutic intervention and lessening potential collateral damage to normal, non-diseased tissue. In its simplest form, PDT is the combination of a photosensitive agent with special forms of illumination to produce a therapeutic response in certain tissues, such as a tumor. The agent attains an excited, active state when it absorbs one or more photons and then is or becomes efficacious. Key elements of a successful PDT regimen include either selective application or selective uptake of a photosensitive agent into the diseased tissue and site-specific application of the activating light. PDT agents are typically applied systemically (for example, via intravenous injection or oral administration) or via localized topical application directly to diseased tissues (for example, via topical creams, ointments, or sprays). Subsequent to administration of the agent (typically 30 minutes to 72 hours later), an activating light is applied to the disease site, locally activating the agent, and destroying the diseased tissue. Light is typically applied by direct illumination of the site, or by delivery of light energy to internal locations using a fiberoptic catheter or similar device.
Most current PDT regimens are based on systemic application of porphyrin-based agents or topical or systemic application of psoralen-based agents. Examples of porphyrin-based agents include porfimer sodium (PHOTOFRIN®), hematoporphyrin-derivative (HPD), benzoporphyrin derivative (BPD), Lutex, BOPP, 5-aminolevulinic acid (ALA), and SnET2. PHOTOFRIN® is one of the few agents currently licensed by the U.S. FDA. Porphyrin-based agents generally are derived from complex mixtures of natural or synthetically prepared materials, and may contain components that are lipophilic. As a possible result of this lipophilicity, porphyrin-based agents have shown a slight tendency to preferentially accumulate in some tumors and other diseased tissues. However, the targeting of such agents to diseased tissue is still unacceptably low when compared to uptake in normal tissue (i.e., at most 2-10× greater uptake in diseased tissue relative to normal tissue). The psoralens, such as 8-MOP, 5-MOP, trioxsalen, and AMT, are nucleic acid intercalators that function by impairing cellular physiology. This intercalation appears to be relatively indiscriminate in terms of tissue type, and as a result these agents also exhibit minimal specificity for diseased tissue. Thus, current agents have failed to exhibit sufficient specificity, and may exhibit additional disadvantages, including persistent systemic or localized photosensitivity, systemic or localized toxicity, and unacceptable treatment cost (due to high agent cost or excessive dosage requirements).
The inherent disadvantages of various current PDT agents and medicaments containing such agents have made acceptable PDT-based treatment of various human and animal conditions difficult or impossible. These disadvantages are particularly serious in the case of indications affecting external or internal surface or near surface tissues, where it would be desirable to have medicaments suitable for localized, selective treatment of the desired tissues. Such indications include a variety of conditions affecting the skin and related organs, the mouth and digestive tract and related organs, the urinary and reproductive tracts and related organs, the respiratory tract and related organs, as well as various other tissue surfaces, such as tissue surfaces exposed during surgery.
Therefore, it is an object of the present invention to provide new medicaments, medical uses for such medicaments based on targeted application of such medicaments and methods for treatment using such medicaments, thereby resulting in increased efficacy and safety and reduced cost of treatment.